This research proposal describes a study of the basic photochemical properties of furocoumarins (psoralens) in order to clarify the chemical basis for their biological activity. Ultimately, this project is expected to provide a foundation of a knowledge necessary for the development of medicinally-useful analogs. Furocoumarins have been used for the treatment of skin disorders for thousands of years. Today, furocoumarins are still widely used as one of the most effective treatments of psoriasis. However, their biological activities in DNA are not completely understood on the basis of the characteristics of furocoumarins in solution. Almost all of these activities of furocoumarins can be attributed to their photochemical reactivity toward DNA. The observed photochemical reactivity of furocoumarins in DNA is very much different from that in solution. The different reactivities in different chemical environments suggest an important contribution of non-bonded interactions in DNA preceding to the photochemical events. In this research project, the factors that govern the photochemical reactivity of furocoumarins will be studied first from the mechanistic viewpoint. Then, model compounds will be synthesized in order to elucidate the nature of important non- bonded interactions in DNA. In these model compounds, two reacting double bonds are covalently connected each other, enabling them to interact intramolecularly. It is anticipated that the proposed research project will provide a key to develop new medicinally-useful analogs.